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What Are Clinical Trials of Medications?
And How Do They Work?

By Kimberly Read & Marcia Purse, About.com Guide

Updated September 10, 2009

About.com Health's Disease and Condition content is reviewed by the Medical Review Board

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Clinical trials of medications are the way new drugs are tested before they can be approved by regulatory agencies such as the Food and Drug Administration (FDA) in the United States. Every new medication must go through a series of clinical trials, which are the last phase of testing before submitting the drug for approval. Based on the data from the clinical trials, the FDA or similar agency in another country may:

Approve the drug for marketing and sale
Require additional clinical trials followed by resubmission for approval
Reject the application

During clinical trials, a new drug (called an investigational medication) is tested for a number of factors, including:

Whether it effectively treats the condition it's supposed to treat
Whether it is safe to use
What the side effects are
How frequent each side effect is
Whether any of the side effects are dangerous
How many people drop out of the study because of side effects

If a drug is intended to treat more than one condition it must go through separate clinical trials for each condition. An example of this is anticonvulsant medications. These must go through separate clinical trials if the manufacturer wants them approved both to treat epilepsy and to be used as mood stabilizers in the treatment of bipolar disorder.

How Are Medication Clinical Trials Set Up?

Clinical trials for medication are closely supervised evaluation by doctors and the manufacturing drug company to determine drugs' safety and effectiveness.

All medication clinical trials must follow a strict set of rules called "protocol." Before any trial begins, the protocol must be reviewed and approved by proper authorities, including an Institutional Review Board (IRB). An IRB is an independent committee of medical and non-medical professionals who together assess a study's potential benefits and risks to ensure that (1) participants are fully informed and (2) their rights and welfare are fully protected.

How Many Clinical Trials Are Needed?

In the United States, there are preclinical trials and 4 phases of human trials. In preclinical trials, the manufacturer determines whether they can reasonably believe the drug is safe and effective. The human trial phases are:

Phase I Trials - very small trials checking risks and side effects.
Phase II Trials - slightly larger trials checking safety and learning about dosages.
Phase III Trials - large trials (may have thousands of participants across the country) gathering information about safety, effectiveness, and the other issues listed at the beginning of this article.
Phase IV Trials - these are also called post-marketing studies and are often required by the FDA after initial approval is given. In these trials, the long-term safety and effectiveness of the medication are checked, and other data about using the drug may be gathered.

In addition, approved drugs may go straight into Phase III trials when the manufacturer wants to get the medication approved for an additional use, as mentioned above.

How Do They Get Accurate Information?

Clinical trials have two factors that help the researchers gather good information about the drug:

The trials are "placebo-controlled." This means that up to half the participants are not receiving the real drug, but instead are being given something that looks just like it but is inactive. (For more, see Placebo.)
The trials are "double-blind." This means that not only do the participants not know whether they are receiving the real medication or a placebo, but the people giving the drug to the participants don't know, either.

These procedures are used because some people will experience improvement or side effects simply because they are in the study and think they may be taking the real medication. For example, the results may show that while 6% of people taking the investigational medication felt drowsy while taking it, 3% of those taking the placebo did as well.

What Is Informed Consent?

Informed consent is the process that potential participants go through before joining the study. They are told of the goals, procedures, anticipated risks and benefits of the study. The informed consent document is a written agreement, signed by participants or their designated representatives, that certifies they have been fully informed about the nature of the research and are willing to participate in the study. Only after a prospective participant is fully informed and signs the informed consent document can he or she enroll in the clinical trial.

What Rights Do Participants Have?

Participants in a clinical trial have certain rights before the study begins and while it is in progress. They are allowed and encouraged to ask questions at any time about the study or medication involved. They are also free to decline to participate and may withdraw from the trial at any time without prejudice or loss of future treatment.

Participants are also entitled to an explanation of any risks, benefits and available alternative treatments, plus any significant findings made during the study that could affect their willingness to continue as a participant.

In addition, clinical trials are each watched by a Data Monitoring Committee. These experts review ongoing information to make sure:

The trial is being conducted in the safest way possible.
Whether the treatment is harmful or has no benefits. In this case, the committee will end the study.
Where two treatments are being compared, if one treatment is clearly shown to be better than the other, the committee will stop the study. In this case, all participants are are offered the better treatment.

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